With the development of human society, chemical industries have been continually developed, thus necessitating the development of chemical analysis technology. The chemical analysis technology commonly designates a method used to identify and detect a specific material, and find out the chemical composition.
For rapid and accurate chemical analysis, a chemical analysis apparatus is under development to automatically perform the chemical analysis instead of a manual chemical analysis that depends on an individual experimenter. In such a chemical analysis apparatus, only if a collected sample is supplied to the apparatus, a total analysis procedure is automatically performed in one system. That is, operations of mixing the sample with reagents, reacting them for a predetermined time, transferring a reactant to a detector, and outputting a signal in proportion to the concentration of a target substance as an electrical or optical signal are automatically carried out in one measuring system.
Recently, an innovative apparatus where an automatic analysis apparatus is finely implemented in a very small-sized chip has been developed, which is called a lab-on-a-chip. The lab-on-a-chip has a fine fluid channel through which a fluid sample is introduced, and then various operations for chemical analysis such as operations of mixing and reacting the fluid sample with reagents, and detecting the reactant are performed within one lab-on-a-chip. The use of the lab-on-a-chip for chemical analysis allows the chemical analysis procedure to be very simplified, and further a pre- or post-treatment before or after the chemical analysis can be omitted because the lab-on-a-chip used once is discarded. A protein lab-on-a-chip or a DNA lab-on-a-chip is put into practical use and being widely used. Herein, the protein lab-on-a-chip is an apparatus of analyzing and measuring a specific protein in blood, and the DNA lab-on-a-chip is an apparatus of analyzing a specific deoxyribonucleic acid (DNA) in a sample.
FIG. 1 is a flowchart and related concept views illustrating a chemical analysis procedure in a lab-on-a-chip. Herebelow, descriptions will be made on a procedure of separating a blood cell from blood and a procedure of analyzing a specific protein included in a portion of a blood plasma component.
Referring to FIG. 1, a blood is injected into a lab-on-a-chip (S10). A biomarker protein 1 in the blood injected into the lab-on-a-chip moves to a first reaction chamber.
The biomarker protein 1 included in a fluid reacts with a carrier particle 2 in the first reaction chamber (S20). Herein, the carrier particle 2 includes a fluorescent substance 3 and a primary antibody 4. The carrier particle 2 may be nanometers or micrometers in size. The carrier particle 2 may be fixed by a scaffold 5, which is provided on a lower substrate 10 of the first reaction chamber and composed of a mucous substance having an adhesive force. A primary antigen-antibody reactant 6 is formed through the primary antigen-antibody reaction between the biomarker protein 1 included in the fluid and the primary antibody 4 included in the carrier particle 2.
The primary antigen-antibody reactant 6 is transferred according as the fluid flows (S30). The primary antigen-antibody reactant 6 transferred by the flow of the fluid reacts with a secondary antibody 8 in a second reaction chamber. A secondary antigen-antibody reactant 9 is formed through the secondary antigen-antibody reaction between the biomarker protein 1 included in the primary antigen-antibody reactant 6 and the secondary antibody 8. The fluorescent image caused by the fluorescent substance 3 contained in the carrier particle 2 is analyzed by irradiating light onto the secondary antigen-antibody reactant 9. Therefore, it is possible to analyze whether a specific protein is contained or not in blood, and the amount of the specific protein.
FIGS. 2 and 3 are conceptual perspective and sectional views illustrating a typical capillary force lab-on-a-chip.
Referring to FIGS. 2 and 3, the typical capillary force lab-on-a-chip includes a lower substrate 10, an upper substrate 20, and side substrates 30 and 40. The lower substrate 10 and the upper substrate 20 are arranged in such a way to have a constant gap h therebetween, thereby forming a capillary. Herein, the mark h means a threshold gap, i.e., the maximum height allowing the capillary to have a capillary force. The capillary forces respectively exist on inner surfaces of the lower substrate 10, the upper substrate and the side substrates 30 and 40.
The lower substrate 10 includes a filter part 12 and hydrophobic grooves 14. The filter part 12 filters an unnecessary component of a fluid sample 50, and passes a specific component selectively. The hydrophobic grooves 14 serve as a timegate delaying the flow of the fluid containing the specific component of the fluid specimen 50. The hydrophobic grooves 14 are obtained through surface-treatment. For example, surfaces of the grooves formed in the lower substrate 10 are surface-treated with hydrophobic substances. Differently from the drawings, the timegate may be achieved by modifying the shape of a channel through which the fluid flows. Such a timegate is used to delay the flow of the fluid to thereby increase the reactivity between the specific component included in the fluid and a reagent.
In the capillary force lab-on-a-chip having a timegate using the hydrophobic grooves, as an inflow rate of the fluid containing the specific component becomes fast, the fluid makes the hydrophobic groove to be wet or the hydrophobicity of the surface of the hydrophobic groove weakened due to the introduction of moisture. Resultantly, the hydrophobic groove does not perform its function, i.e., a timegate function, and thus a portion of the specific component included in the fluid does not react well with the reagent to be used for analysis.
Furthermore, in the capillary force lab-on-a-chip having the timegate using a shape modification of a fluid channel, the shape of the fluid channel is too complicated, which leads to a difficulty in fabrication. Also, the complicated shape of the fluid channel makes the channel length to be increased, thus causing a total size of the capillary force lab-on-a-chip to be increased.
In addition, since the timegate using the shape modification of the fluid channel or the hydrophobic grooves plays only a role in delaying the flow of the fluid, it is difficult to precisely control the reactivity between the specific component contained in the fluid specimen and the reagent.